Palosuran

Palosuran (ACT-058362) is a potent, selective, and orally active antagonist of urotensin II receptor, with an IC₅₀ of 3.6 nM for CHO cell membranes expressing human recombinant receptors. Palosuran can improves pancreatic and renal function in diabetic rats^[1][2]. IC50 & Target: IC50: 3.6 nM (human urotensin II receptor)^[1] In Vitro: Palosuran (8 h) inhibits ¹²⁵I-U-II binding to human UT receptor, with IC₅₀s of 46.2 nM on TE 671 cells and 86 nM on recombinant CHO cells^[1].
Palosuran inhibits Ca²⁺ mobilization in response to human U-II in CHO cells expressing human and rat UT receptor with IC₅₀s of 17 and >10000 nM, respectively^[1].
Palosuran (0.12-10000 nM; 20 min) inhibits human U-II induced MAPK phosphorylation in a dose-dependent manner in recombinant CHO cells, with an IC₅₀ of 150 nM^[1]. In Vivo: ACT-058362 (10 mg/kg/h; i.v.) fully prevents the decrease in renal blood flow after ischemia in rats without decreasing blood pressure^[1].
Palosuran (300 mg/kg/d; p.o. for 16 weeks) improves the survival, increases insulin, and slows the increase in glycemia, glycosylated hemoglobin, and serum lipids in streptozotocin-induced diabetic rats^[2].